Next-generation sequencing: emerging lessons on the origins of human cancer.

This review describes recent advances in technologies for massive parallel sequencing of human genomes and discusses their application to the analysis of cancer genomes. Several different instruments are now available for next-generation sequencing (NGS). Although they use different sample preparation and sequencing technologies, they all rely on large computing capacity for assembling sequences and identifying somatic mutations against the background of genetic variations. Recent examples of NGS application to cancer genomes include the sequencing of 22 cases of glioblastoma multiforme that identified IDH1, the gene encoding isocitrate dehydrogenase 1, as target for cancer-driving mutations. Analysis of entire genomes of single samples of lung cancer and melanoma has brought unprecedented details on how tobacco carcinogens and UV exposure, respectively, may sculpt specific mutation landscapes. In breast cancer, comparative genome sequencing of primary and secondary lesions of a single patient has revealed clues on the phylogeny of tumor cells. NGS is opening a new era for understanding how environmental factors alter the human genome to generate cancerous cells, paving the way to a better understanding of the origins of human cancer.